LRRK2 gene mutations are a common cause of Parkinsons disease. The protein product of the gene has both kinase and GTPase activities. Because there are mutations in both kinase and GTPase domains, we consider that both activities are probably important for pathogenesis of Parkinsons disease. As such, we are trying to understand each activity in turn and how they interact. We have particularly been focussing in this project, and in related projects, on what LRRK2 can interact with as we suspect that the GTPase activity of LRRK2 is important in strength of protein-protein interactions. We have published screens for interacting partners of LRRK2 and the related protein LRRK1. We found that there were common interacting proteins but also distinct ones, which suggest each protein has a distinct role within the cell. Following on from these observations, our current work is particularly focussed on the normal function of LRRK2. We are using LRRK2 knockout mice to examine the proteome in tissues that have or lack the homologue LRRK1.